Tag Archives: hypothermia

Many clinicians extrapolate adult research findings to paediatric patients because there’s no alternative, and until now we’ve had to do that with post-cardiac arrest therapeutic hypothermia after paediatric cardiac arrest.

However the THAPCA trial in the New England Journal of Medicine now provides child-specific data.

It was a multicentre trial in the US which included children between 2 days and 18 years of age, who had had an out-of-hospital cardiac arrest and remained comatose after return of circulation. They were randomised to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C) within 6 hours after the return of circulation.

Therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit with respect to survival with good functional outcome at 1 year, and survival at 12 months did not differ significantly between the treatment groups.

These findings are similar to the adult TTM trial, although there are some interesting differences. In the paediatric study, the duration of temperature control was longer (120 hrs vs 36 hrs in the adult study), respiratory conditions were the predominant cause of paediatric cardiac arrest (72%), and there were only 8% shockable rhythms in the paediatric patients, compared with 80% in the adult study.

Background: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.

Methods: We conducted this trial of two targeted temperature interventions at 38 children’s hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.

Results: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.

Conclusions: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year.

The focus of the entire day is cardiac arrest and this is the second day of the London Cardiac Arrest Symposium.

Professor Niklas Nielsen kicked off with a presentation of his Targeted Temperature Management trial. It seems that even now there is uncertainty in the interpretation of this latest study. I take heart from the knowledge that Prof Nielsen has changed the practice of his institution to reflect the findings of his study – I have certainly changed my practice. But we need to remain aware that there is more work to be done to answer the multiple questions that remain and the need for further RCTs is recognised.

The management of Cardiac arrest after avalanche is not a clinical scenario that I imagine I’ll ever find myself in. The management is well documented in the ICAR MEDCOM guidelines 2012. Dr Peter Paal reminded us that you’re not dead until you’re rewarmed and dead unless: with asystole, CPR may be terminated (or withheld) if a patient is lethally injured or completely frozen, the airway is blocked and duration of burial >35 min, serum potassium >12 mmol L(-1), risk to the rescuers is unacceptably high or a valid do-not-resuscitate order exists.

The age old question about prognostication after cardiac arrest was tackled by Prof Mauro Oddo. He covered the evidence for clinical examination, SSPE, EEG, and neurone specific enolase. Bottom line, all of these modalities are useful but none are specific enough to be used as a stand alone test so multiple modalities are required.

SAMU is leading the way with prehospital ECMO. They have mastered the art of cannulation (in the Louvre no less!) but there haven’t enough cases to demonstrate a mortality benefit. The commencement of ECMO prehospital reduces low flow time and theoretically should improve outcomes. This is begging for a RCT.

The experience of the Italians with in hospital ECMO shoes a better survival rate for in-hospital rather than out of hospital cardiac arrests, explained Dr Tomasso Mauri. They treat patients with a no flow time of <6min and low flow rate of <45min and had a 31% ICU survival rate. If you want to learn more about ED ECMO go to http://edecmo.org.

In cardiac arrest the aim is to improve coronary perfusion, to preserve perfusion to the heart and the brain, offer a route of rapid temperature control and offer a direct route of administration of adrenaline. Coronary perfusion is seen to be supra normal after SAAP. And the suggested place for SAAP is prior to ECMO.

It’s more familiar ground talking about SAAP in trauma. This Zone 1 occlusion preserves cerebral and cardiac perfusion while blood loss is limited and rapid fluid resuscitation can occur.

Patients in cardiac arrest due to severe hypothermia benefit from extracorporeal rewarming, and it is often recommended that they are treated at centres capable of providing cardiopulmonary bypass or extracorporeal membrane oxygenation (ECMO).

But what if they’re brought to a centre that doesn’t have those facilities?

If you work in such a centre do you have a plan, and are you familiar with what equipment you could use?

One option if you have an ICU is to provide extracorporeal warming using a haemofiltration machine used for renal replacement therapy(1). A double lumen haemofiltration catheter is inserted into a central vein and an ICU nurse can often do the rest, although some variables have to be set by the intensivist, often aided by a standard renal replacement therapy prescription chart. The machines are mobile and can be wheeled into the resus room (I have practiced this set up in resus). It might be worth discussing and practicing this option with your ICU.

Another extracorporeal option is to rig up a rapid infusion device such as a ‘Level 1’ to connect to arterial and venous catheters so that blood from the patient flows through and is warmed by the machine before being returned to the patient(2). Rapid rewarming has been achieved by this method but it requires some modification to the usual set up and so is much less likely to be a realistic option for most teams doing this on very rare occasions.

Less technical options are the traditionally taught warm saline lavage of body cavities such as the thorax and the peritoneal cavity. These can be achieved with readily available catheters and of course should be combined with ventilation with warmed gas and administration of warm intravenous fluid.

Thoracic lavage can be achieved with open thoracotomy or tube thoracostomy. One or two chest tubes can be placed on each side. One technique was described as:

Two 36 French chest tubes were placed in each hemithorax. One tube was placed in the fourth intercostal space in the mid-clavicular line. Another tube was placed into the sixth intercostal space in the mid-axillary line. Sterile saline at 39.0◦C was infused by gravity into each superior chest tube and allowed to drain passively through each inferior tube.(3)

Rapid rewarming at a rate of 6.8◦C per hour was achieved in an arrested hypothermic man using peritoneal lavage. It was done in the operating room with peritoneal lavage (saline 40◦C) with a rapid infusion system (Level 1) through two laparoscopic access sites. It was combined with external forced air rewarming and warm intravenous infusions(4).

Finally some devices manufactured for inducing hypothermia in post-cardiac arrest patients can also be used to rewarm patients, which might be endovascular devices, such as the Cool Line® catheter(5), or external, such as the Arctic Sun® Temperature Management System(6). It’s definitely worth finding out what your critical care services have as far as this equipment goes.

In summary, although the ‘exam answer’ for cardiac arrest due to profound hypothermia is often ECMO/cardiopulmonary bypass, in most centres that’s not an option. It’s helpful to remind ourselves that (1) other extracorporeal rewarming options exist and (2) non-extracorporeal techniques can provide rapid rewarming.

I am impressed with those investigators who had the wherewithall to subject previous therapeutic hypothermia studies to skeptical scrutiny and then design and conduct a robust multicentre trial to answer the question.

One of the criticisms of the original two studies was that those patients who were not actively cooled did not have their temperature tightly controlled, and therefore some were allowed to become hypERthermic, which is bad for brains.

This latest study showed no difference in survival or neurological outcome after cardiac arrest between target temperatures of 33°C and 36°C.

So controlling the temperature after cardiac arrest is still important, but cooling down to the recommended range of 32-4°C is not.

BACKGROUND Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.

METHODS In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.

RESULTS In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.

CONCLUSIONS In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

This small study supports the hypothesis that therapeutic hypothermia can have positive inotropic effects in patients with cardiogenic shock of ischaemic or non-ischaemic origin.

Cooling resulted in a temperature-dependent decrease in heart rate and temperature-dependent increases in stroke volume index, cardiac index, mean arterial pressure, and cardiac power output. These changes reversed when the patients were rewarmed.

The authors summarise as follows:

In summary, our studies demonstrate that moderate hypothermia is feasible and safe also for patients in cardiogenic shock.

Improved cardiac performance may contribute to the considerable decrease of mortality for survivors of cardiac arrest, and the use of hypothermia can be recommended for patients with a clear indication for cooling and poor cardiac performance.

Moreover, hypothermia might be considered as a positive inotropic intervention during cardiogenic shock.

AIM OF THE STUDY: Hypothermia exerts profound protection from neurological damage and death after resuscitation from circulatory arrest. Its application during concomitant cardiogenic shock has been discussed controversially, and still hypothermia is used with reserve when haemodynamic parameters are impaired. On the other hand hypothermia improves force development in isolated human myocardium. Thus, we hypothesized that hypothermia could beneficially affect cardiac function in patients during cardiogenic shock.

METHODS: 14 Patients, admitted to Intensive Care Unit for cardiogenic shock under inotropic support, were enrolled and moderate hypothermia (33°C) was induced for either one (n=5, short-term) or twenty-four (n=9, mid-term) hours.

RESULTS: 12 patients suffered from ischaemic cardiomyopathy, 2 were female, and 6 were included after cardiac arrest and resuscitation. Body temperature was controlled by an intravascular cooling device. Short-term hypothermia consistently decreased heart rate, and increased stroke volume, cardiac index and cardiac power output. Metabolic and electrocardiographic parameters remained constant during cooling. Improved cardiac function persisted during mid-term hypothermia, but was reversed during re-warming. No severe or persistent adverse effects of hypothermia were observed.

CONCLUSION: Moderate Hypothermia is safe and feasable in patients during cardiogenic shock. Moreover, hypothermia improved parameters of cardiac function, suggesting that hypothermia might be considered as a positive inotropic intervention rather than a risk for patients during cardiogenic shock.

You receive a patient resuscitated from cardiac arrest to a perfusing rhythm in your emergency department. History suggests a long ‘down time’: There was a ten minute duration of ‘no-flow’ (time from collapse to the start of resuscitation attempts).

Would this make you more likely or less likely to initiate targeted temperature management (TTM) and cool the patient to the recommended 32-34 degrees?

A recent study supports the suggestion that a longer no-flow time is associated with greater odds of survival with TTM compared with no TTM, than patients with shorter no-flow times. In other words, cooling the patient is more likely to make a difference in the ‘long down time’ patient, even though the overall survival in that group is obviously less.

Aim Mild therapeutic hypothermia has shown to improve long-time survival as well as favorable functional outcome after cardiac arrest. Animal models suggest that ischemic durations beyond 8 min results in progressively worse neurologic deficits. Based on these considerations, it would be obvious that cardiac arrest survivors would benefit most from mild therapeutic hypothermia if they have reached a complete circulatory standstill of more than 8 min.

Methods In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest, which remain comatose after restoration of spontaneous circulation. Data were collected from 1992 to 2010. We investigated the interaction of ‘no-flow’ time on the association between post arrest mild therapeutic hypothermia and good neurological outcome. ‘No-flow’ time was categorized into time quartiles (0, 1–2, 3–8, >8 min).

Results One thousand-two-hundred patients were analyzed. Hypothermia was induced in 598 patients. In spite of showing a statistically significant improvement in favorable neurologic outcome in all patients treated with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.14–1.93) this effect varies with ‘no-flow’ time. The effect is significant in patients with ‘no-flow’ times of more than 2 min (OR: 2.72; CI: 1.35–5.48) with the maximum benefit in those with ‘no-flow’ times beyond 8 min (OR: 6.15; CI: 2.23–16.99).

Conclusion The beneficial effect of mild therapeutic hypothermia increases with cumulative time of complete circulatory standstill in patients with witnessed out-of-hospital cardiac arrest.

As the authors of this study point out, the reliability of tympanic temperature monitoring is still under debate. Since invasive measures of core temperature employed in the ICU may not be practicable in the pre-hospital setting, it would be helpful to employ a simpler method in the field, particular if we are implementing targeted temperature management post-cardiac arrest. In this small study of ten patients (with 558 temperature measurements) there was a high degree of correlation between tympanic and oesophageal temperature (r=0.95, p<0.0001, 95% CI 0.93 to 0.96) and also between tympanic and bladder temperature (r=0.96, p<0.0001, 95% CI 0.95 to 0.97). This finding is apparently in keeping with results obtained from patients undergoing cardiac surgery.

Objective Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non-invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia.

Methods Ten consecutive patients admitted to our medical intensive care unit after out-of-hospital cardiac arrest were included in this study. During MTH, tympanic temperature was measured using a digital thermometer. Simultaneously, oesophageal and bladder temperatures were recorded in a total of 558 single measurements.

Results Compared with oesophageal temperature, bladder temperature had a bias of 0.019°C (limits of agreement ±0.61°C (2SD)), and tympanic measurement had a bias of 0.021°C (±0.80°C). Correlation analysis revealed a high relationship for tympanic versus oesophageal temperature (r=0.95, p<0.0001) and also for tympanic versus bladder temperature (r=0.96, p<0.0001).

Conclusions That tympanic temperature accurately indicates both oesophageal and bladder temperatures with a very small discrepancy in patients undergoing MTH after cardiac arrest is demonstrated in this study. Although our results were obtained in the hospital setting, these findings may be relevant for the prehospital application of therapeutic hypothermia as well. In this case, tympanic temperature may provide an easy and non-invasive method for temperature monitoring.

Okay – rather than ‘therapeutic hypothermia’, the recommended phrase now is ‘targeted temperature management’. Several critical care authorities got together to produce clinical recommendations on this topic. Here are a few interesting points from the document:

On coagulation:Hypothermia affects platelet function and prolongs the prothrombin time and partial thromboplastin time. These effects are masked when laboratory analysis is performed at 37°C, suggesting that any risk will be mitigated by rewarming.

Although not mentioned in the abstract, the authors examined the role of TTM in raised intracranial pressure (ICP):Sufficient evidence exists to conclude that TTM does decrease ICP compared to unstructured temperature management. However, there is no sufficient evidence to make a recommendation regarding the use of targeted hypothermia to control elevated ICP to improve patent-important outcomes in TBI. The jury makes NO RECOMMENDATION regarding the use of TTM as an ICP control strategy to improve outcomes in brain injuries regardless of cause (trauma, hemorrhage, or ischemic stroke).

Regarding acute liver failure with severe cerebral edema:there are currently no RCTs. There is a case series suggesting a strongly favorable effect. This is a powerful argument for support of an RCT evaluating TTM alone or in combination with hepatic dialysis strategies

OBJECTIVE: Representatives of five international critical care societies convened topic specialists and a nonexpert jury to review, assess, and report on studies of targeted temperature management and to provide clinical recommendations.

DATA SOURCES: Questions were allocated to experts who reviewed their areas, made formal presentations, and responded to questions. Jurors also performed independent searches. Sources used for consensus derived exclusively from peer-reviewed reports of human and animal studies.

STUDY SELECTION: Question-specific studies were selected from literature searches; jurors independently determined the relevance of each study included in the synthesis.

CONCLUSIONS AND RECOMMENDATIONS:

The jury opines that the term “targeted temperature management” replace “therapeutic hypothermia.”

The jury opines that each report of a targeted temperature management trial enumerate the physiologic effects anticipated by the investigators and actually observed and/or measured in subjects in each arm of the trial as a strategy for increasing knowledge of the dose/duration/response characteristics of temperature management. This enumeration should be kept separate from the body of the report, be organized by body systems, and be made without assertions about the impact of any specific effect on the clinical outcome.

The jury STRONGLY RECOMMENDS targeted temperature management to a target of 32°C-34°C as the preferred treatment (vs. unstructured temperature management) of out-of-hospital adult cardiac arrest victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation, moderate quality of evidence).

The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33°C-35.5°C (vs. less structured management) in the treatment of term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy (weak recommendation, moderate quality of evidence).

Predicting neurological recovery after successful cardiac arrest resuscitation has always been tricky, with clinical signs on day one being unreliable, but absent pupillary responses or absent or extensor motor responses to painful stimuli being predictive of a poor outcome on day three. However, the use of therapeutic hypothermia, and its frequent associated need for sedation, appear to make even these downstream assessments inclined to give false positive predictions for a poor outcome, potentially resulting in withdrawal of intensive care in patients who may have recovered. A review recommends a multimodal approach to prognostication.

Regarding physical examination, the authors state:
In summary, therapeutic hypothermia and sedation required for induced cooling might delay recovery of motor reactions up to 5–6 days after cardiac arrest. Corneal/ pupillary reflexes and myoclonus are more robust predic- tors of poor outcome after cardiac arrest, but their absence is not an absolute predictor of dismal prognosis

PURPOSE OF REVIEW: Therapeutic hypothermia and aggressive management of postresuscitation disease considerably improved outcome after adult cardiac arrest over the past decade. However, therapeutic hypothermia alters prognostic accuracy. Parameters for outcome prediction, validated by the American Academy of Neurology before the introduction of therapeutic hypothermia, need further update.RECENT FINDINGS: Therapeutic hypothermia delays the recovery of motor responses and may render clinical evaluation unreliable. Additional modalities are required to predict prognosis after cardiac arrest and therapeutic hypothermia. Electroencephalography (EEG) can be performed during therapeutic hypothermia or shortly thereafter; continuous/reactive EEG background strongly predicts good recovery from cardiac arrest. On the contrary, unreactive/spontaneous burst-suppression EEG pattern, together with absent N20 on somatosensory evoked potentials (SSEP), is almost 100% predictive of irreversible coma. Therapeutic hypothermia alters the predictive value of serum markers of brain injury [neuron-specific enolase (NSE), S-100B]. Good recovery can occur despite NSE levels >33 μg/l, thus this cut-off value should not be used to guide therapy. Diffusion MRI may help predicting long-term neurological sequelae of hypoxic-ischemic encephalopathy.SUMMARY: Awakening from postanoxic coma is increasingly observed, despite early absence of motor signs and frank elevation of serum markers of brain injury. A new multimodal approach to prognostication is therefore required, which may particularly improve early prediction of favorable clinical evolution after cardiac arrest.Predicting neurological outcome after cardiac arrest

More data on the RhinoChill device from an in-hospital study of post-cardiac arrest patients in Germany. The RhinoChill device (BeneChill Inc., San Diego, USA) allows evaporative cooling by spraying an inert liquid coolant (a perfluorochemical) into the nasal cavity. The liquid evaporates instantaneously, thereby removing heat. It can make your nose discoloured, and in one patient with cardiogenic shock, tissue damage of nose and cheeks due to freezing occurred. Several of the authors are linked with the company that manufactures the device.

METHODS: Eleven emergency departments and intensive care units participated in this multi-centre, single-arm descriptive study. Eighty-four patients after successful resuscitation from cardiac arrest were cooled with nasopharyngeal delivery of an evaporative coolant for 1h. Subsequently, temperature was controlled with systemic cooling at 33 degrees C. Cooling rates, adverse events and neurologic outcome at hospital discharge using cerebral performance categories (CPC; CPC 1=normal to CPC 5=dead) were documented. Temperatures are presented as median and the range from the first to the third quartile.